Normally, uracil-DNA glycosylase (UNG) is a DNA repair protein that protects the human genome and other organisms from damage. Water converts the normal DNA link, cytosine, to uracil and this can lead to mutations and cell death. UNG constantly monitors and corrects this damage. However, in cancer cells DNA repair interferes with chemotherapy and in many dangerous infections UNG from bacteria and viruses increases their virulence. 吃瓜官网 scientists, together with researchers from MSU, and the HSE University, a library of 1,027,767 ligands and found a new promising pharmacophore that inhibits uracil-DNA glycosylase. This can be included in complex preparations for antitumor, antiviral, and antibacterial therapy.
During the first stage, Moscow scientists selected 378 potentially active ligands using computer analysis of spatial structures. Later, based on this data, Novosibirsk researchers took 19 potentially active and 4 potentially inactive chemical compounds and evaluated their ability to interfere with the activity of human UNG and vaccinia virus.
Dmitry Zharkov, Doctor of Biological Sciences, Corresponding Member of the Russian Academy of Sciences, Professor of the NSU talked about this research,
In the course of our experiments, we found that compounds that inhibit the UNG enzyme with varying degrees of effectiveness have a common fragment, tetrahydro-2,4,6-trioxopyrimidinylidene. In pharmacology, fragments that are responsible for the activity of a drug are called pharmacophores. Our active fragment turned out to be new and unique. Existing UNG inhibitors are based on compounds with a different spatial structure. With this pharmacophore as a base, is it possible to engage in further research to create drugs and improve their characteristics (effect, assimilation by the body, etc.).
